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Singh M.,Punjabi University | Singh P.,Punjabi University | Singh S.,Aggarwal Orthopedic Hospital | Juneja P.K.,Aggarwal Orthopedic Hospital | Kaur T.,Amrit Sagar Hospital
Journal of Bone and Mineral Metabolism | Year: 2013

The influence of the coordinated effect of various single-nucleotide polymorphisms (SNPs) within the endothelial nitric oxide synthase (eNOS) gene on the risk of osteoporosis in hypertension has remained undetermined. Four pertinent SNPs of the eNOS gene, rs2070774, rs1799983, rs1800780 and rs3918181, were examined for the risk of osteoporosis in 313 hypertensive postmenopausal women in Northwest India. All the hypertensive women were verified with dual energy X-ray absorptiometry and categorized as 150 with osteoporosis and 163 without osteoporosis. The minor allele (T) of rs1799983 exerts a statistically significant risk for osteoporosis both in dominant [odds ratio (OR) 3.71, 95 % confidence interval (CI) 2.12-6.49, P < 0.001] and recessive mode (OR 5.75, 95 % CI 1.24-26.69, P = 0.036) after Bonferroni correction. Bone mineral density (BMD) values (corrected for the effects of risk variables) according to eNOS SNP genotypes revealed a significant association with rs1799983 at both the lumbar spine (P = 0.001) and femoral neck (P = 0.023). Risk association analyses revealed a susceptibility haplotype TTAG which influences the risk of osteoporosis (OR 2.02, 95 % CI 1.05-3.39, P = 0.042) in hypertension after adjusting for the effects of risk factors. Furthermore, this haplotype was significantly associated with BMD at the lumbar spine (P = 0.029) and femoral neck (P = 0.021) in a dose-dependent manner. The results suggest that possession of the TTAG haplotype of the eNOS gene may increase the risk of osteoporosis two-fold in hypertensive postmenopausal women in Northwest India. © 2013 The Japanese Society for Bone and Mineral Research and Springer Japan.


Singh M.,Punjabi University | Singh P.,Punjabi University | Singh S.,Aggarwal Orthopedic Hospital | Juneja P.K.,Aggarwal Orthopedic Hospital | Kaur T.,Amrit Poly Clinic
Maturitas | Year: 2010

Background: The association of apolipoprotein E (APOE) genotypes with bone mineral density (BMD) and risk of osteoporosis have remained unclear. The influence of APOE gene polymorphisms on BMD as genetic mediators of osteoporosis risk needs to be explored in Indian postmenopausal females where this disease is rising rampantly. Methods and results: The present study investigated the role and relevance of four pertinent APOE single nucleotide polymorphisms: 5′UTR G/C (rs440446), Int2 G/A (rs769450), Exon4 T/C (rs429358), Exon4 C/T (rs7412) in DEXA verified 133 osteoporotic, 57 osteopenic and 83 normal postmenopausal females of India, who were not taking hormone replacement therapy. Minor allele frequencies of rs440446 and rs429358 were higher in osteoporotic females (0.31, 0.18) than osteopenic (0.29, 0.15) and females having normal bone mass (0.16, 0.07). Disease association analysis revealed a susceptibility haplotype CGTC (in order of rs440446, rs769450, rs429358, rs7412) and the carriers of this haplotype has higher risk of osteopenia (OR 3.53, 95% CI 1.21-11.0, P = 0.017) and osteoporosis (OR 3.61, 95% CI 1.53-9.48, P = 0.002) after adjusting the confounding effect of age, BMI and years since menopause. Females who possess either one copy or two copies of the haplotype have lesser BMD values of lumbar spine (0.88 and 0.85 g/cm2) and femoral neck (0.84 and 0.82 g/cm2) than those females who possess zero copy (0.9 and 0.87 g/cm2, respectively). Conclusions: The present study exposed a susceptibility haplotype CGTC, within APOE gene, which was found to be associated with BMD and risk of osteopenia and osteoporosis in postmenopausal females of India. © 2010 Elsevier Ireland Ltd.


Singh M.,Punjabi University | Singh P.,Punjabi University | Singh S.,Aggarwal Orthopedic Hospital | Juneja P.K.,Aggarwal Orthopedic Hospital | Kaur T.,Amrit Sagar Hospital
Archives of Osteoporosis | Year: 2013

The influence of VDR gene for the risk of osteoporosis has remained inconclusive. VDR gene polymorphism in relation to BMD in postmenopausal women of Northwest India revealed a susceptibility haplotype AGT. Possession of this haplotype exacerbates the risk of osteoporosis by 2.8 times, which manifests in recessive mode of inheritance. Purpose: The purpose of this study is to understand the influence of coordinated effect of various single nucleotide polymorphisms (SNPs) within vitamin D receptor (VDR) gene for the risk of osteoporosis, which has remained undefined so far. Methods: Four pertinent SNPs of VDR gene, i.e., rs2228570, rs1544410, rs17879735, and rs731236 were examined with polymerase chain reaction-restriction fragment length polymorphism in dual energy X-ray absorptiometry verified 188 osteoporotics, 115 osteopenics, and 147 normal postmenopausal women of Northwest India. Results: Minor allele 'T' of rs2228570 showed significant influence for the risk of osteoporosis (OR 1.60, 95%CI 1.16-2.20, P = 0.004) and also in dominant (OR 2.32, 95%CI 1.47-3.64, P = 0.0006) and additive model (OR 2.41, 95%CI 1.49-3.87, P = 0.0006) after Bonferroni correction. Minor allele (T) of rs2228570 showed an allele dose effect with BMD of L1-L4 (P = 0.009) and FN (P = 0.036). Disease association analysis exposed a susceptibility haplotype AGT which influences the risk of osteopenia (OR 2.04, 95%CI 1.03-4.08, P = 0.036) and osteoporosis (OR 2.90, 95%CI 1.61-5.38, P = 0.00005) after adjusting the effects of age, BMI and years since menopause. This haplotype is significantly associated with BMDs at lumbar spine (P = 0.0001) and femoral neck (P = 0.016). Conclusion: In-depth analysis of this haplotype with other methods of Wald statistics and Akaike information criterion confirmed that carriers of each unit of this haplotype AGT increases the risk of osteoporosis by a factor of 2.80 ± 0.34 (β ± SE) which manifests (P = 0.1 × 10-6) in its recessive mode of inheritance. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

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